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Correlation of PAF-AH activity with age (A), HbA1c (B), HDL (C) and LDL (D) in patients with type 1 diabetes mellitus.
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OBJECTIVE: To evaluate platelet-activating factor acetylhydrolase (PAF-AH) activity and its relationship with clinical and demographic variables, metabolic control, apolipoprotein A and B levels and the susceptibility of low-density lipoprotein (LDL) to in vitro oxidation in patients with type 1 diabetes mellitus (DM 1). METHODS: Forty two patients...
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Context 1
... observed significant data with: age (r=0.328; p=0.034), HbA1c (r=-0.319; p=0.039), HDL (r=-0.348; p=0.028) and LDL (r=0.324; p=0.041) (Fig. 3). The stepwise multiple regression using PAF-AH activity as a dependent variable and age, gender, BMI, HbA1c, HDL and LDL as independent variables showed HDL and LDL as independent explanatory variables of changes in PAF-AH activity (step 1: r = 0.231, r2 studied, Cavallo-Perin et al 28 and Nathan et al 27 demonstrated that PAF levels ...
Citations
Aim:
To assess the relevance of lipoprotein-associated phospholipase A2 as a prognostic marker for microvascular diseases.
Methods:
We analysed lipoprotein-associated phospholipase A2 activity and lysophosphatidylcholine levels (as a surrogate marker of oxidative stress) in 165 adolescents (aged 17.0 ± 2.3 years) with a history of Type 1 diabetes greater than 10 years. Clinical data were obtained from the German/Austrian nationwide Diabetes Prospective Follow-up registry at blood collection and on average 2.4 ± 1.3 years later at follow-up. Relationships between lipoprotein-associated phospholipase A2 activity and clinical, demographic and laboratory variables, lysophosphatidylcholine levels and presence of albuminuria were evaluated by multivariable linear and logistic regression.
Results:
Lipoprotein-associated phospholipase A2 activity was higher in male than female adolescents (P = 0.002). Albuminuria was present in 14% (22/158) of participants at baseline, and 5% (4/86) of participants without albuminuria at baseline developed albuminuria until follow-up. Lipoprotein-associated phospholipase A2 activity was associated neither with present nor with incident albuminuria. Lysophosphatidylcholine did not correlate with lipoprotein-associated phospholipase A2 activity. Cross-sectional bivariate correlation as well as multivariable linear regression analysis revealed a negative correlation of lipoprotein-associated phospholipase A2 activity with HbA1c and HDL-cholesterol.
Conclusions:
Lipoprotein-associated phospholipase activity was not associated with surrogate markers for oxidative stress and early diabetic nephropathy. The association of decreased lipoprotein-associated phospholipase A2 activity with poor glucose control might limit its function as a predictor of micro- and macrovascular diseases in Type 1 diabetes. This article is protected by copyright. All rights reserved.
Background:
Inflammation and hypercholesterolaemia contribute to atherosclerotic changes which can start in childhood. Children with hyperlipidaemias are at high-risk for early coronary atherosclerosis. This study evaluates the relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2), carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD) in hypercholesterolaemic dyslipidaemic (HD) children.
Methods:
We performed a case-control study consisting of 43 cases, aged 2 to 17 years, and 24 age-matched controls. Fasting blood samples were obtained from both groups for the measurement of a lipid profile (total cholesterol-TC, LDL-C, HDL-C and triglycerides), and Lp-PLA2 in mass units. The latter was determined with a turbidimetric immunoassay method (PlacTest, DiaDexus Inc.) applied to an automated analyzer. CIMT and FMD measurements were undertaken by a paediatric cardiologist, using high-resolution B-mode ultrasonography.
Results:
TC, LDL-C, and Lp-PLA2 concentrations were significantly higher in the cases than in the controls (P<0.001 for all three parameters). Whilst CIMT values were also significantly higher in the patients compared to the controls (P=0.001), FMD values were significantly lower (P=0.001). We found positive correlations between Lp-PLA2 and TC (r=0.41, P=0.001), Lp-PLA2 and LDL-C (r=0.36, P=0.004), Lp-PLA2 and CIMT (r=0.44, P=0.019), and LDL-C and CIMT (r=0.41, P=0.032); there were negative correlations between Lp-PLA2 and FMD (r=-0.15, P=0.045), TC and FMD (r=-0.45, P=0.017), LDL-C and FMD (r=-0.51, P=0.006), and CIMT and FMD (r=-0.45, P=0.016).
Conclusion:
Lp-PLA2 concentrations are significantly elevated in HD children. Given the association of Lp-PLA2 with markers of atherosclerosis (TC, LDL-C, CIMT, and FMD), the finding of increased concentrations of Lp-PLA2 could be used to identify early atherosclerotic changes in HD children and may inform their clinical management.
Key words:
hypercholesterolaemia, hyperlipidaemia, children, atherosclerosis, Lp-PLA2, carotid intima-media thickness, flow-mediated dilatation.
Lipoprotein associated phospholipase A 2 (Lp-PLA 2 ) is an important risk predictor of coronary artery disease (CAD). This study was aimed to evaluate Lp-PLA 2 activity and oxidized low density lipoprotein (oxLDL) in newly diagnosed patients of type 2 diabetes mellitus and to determine the correlation of Lp-PLA 2 activity with oxLDL and plasma glucose levels.
Blood samples were collected in patients with newly diagnosed type 2 diabetes (n=40) before any treatment was started and healthy controls (n=40). These were processed for estimating plasma glucose: fasting and post prandial, ox LDL, and Lp-PLA2 activity. The parameters in the two groups were compared. Correlation between different parameters was calculated by Pearson correlation analysis in both groups.
Lp-PLA 2 activity (24.48 ± 4.91 vs 18.63 ± 5.29 nmol/min/ml, P<0.001) and oxLDL levels (52.46 ± 40.19 vs 33.26 ± 12.54 μmol/l, P<0.01) were significantly higher in patients as compared to those in controls. Lp-PLA 2 activity correlated positively with oxLDL in both controls (r=0.414, P<0.01), as well in patients (r=0.542, P<0.01). A positive correlation between Lp-PLA 2 activity and fasting plasma glucose levels was observed only in patients (r=0.348, P<0.05).
Result of this study implies that higher risk of CAD in patients with diabetes may be due to increase in Lp-PLA 2 activity during the early course of the disease. A positive correlation between enzyme activity and fasting plasma glucose indicates an association between hyperglycaemia and increased activity of Lp-PLA2. This may explain a higher occurrence of CAD in patients with diabetes. A positive correlation between oxLDL and Lp-PLA2 activity suggests that Lp-PLA2 activity may be affected by oxLDL also.
Background
Lipoprotein-associated phospholipase A2 activity (Lp-PLA2) is a good marker of cardiovascular risk in adults. It is strongly associated with stroke and many others cardiovascular events. Despite this, the impact of obesity on this enzyme activity and its relation to biomarkers of cardiovascular disease in adolescents is not very well investigated. The purpose of this article is to evaluate the influence of obesity and cardiometabolic markers on Lp-PLA2 activity in adolescents.
Results
This cross-sectional study included 242 adolescents (10–19 years) of both gender. These subjects were classified in Healthy Weight (n = 77), Overweight (n = 82) and Obese (n = 83) groups. Lipid profile, glucose, insulin, HDL size, LDL(−) and anti-LDL(−) antibodies were analyzed. The Lp-PLA2 activity was determined by a colorimetric commercial kit. Body mass index (BMI), waist circumference and body composition were monitored. Food intake was evaluated using three 24-hour diet recalls. The Lp-PLA2 activity changed in function to high BMI, waist circumference and fat mass percentage. It was also positively associated with HOMA-IR, glucose, insulin and almost all variables of lipid profile. Furthermore, it was negatively related to Apo AI (β = −0.137; P = 0.038) and strongly positively associated with Apo B (β = 0.293; P < 0.001) and with Apo B/Apo AI ratio (β = 0.343; P < 0.001). The better predictor model for enzyme activity, on multivariate analysis, included Apo B/Apo AI (β = 0.327; P < 0.001), HDL size (β = −0.326; P < 0.001), WC (β = 0.171; P = 0.006) and glucose (β = 0.119; P = 0.038). Logistic regression analysis demonstrated that changes in Apo B/Apo AI ratio were associated with a 73.5 times higher risk to elevated Lp-PLA2 activity.
Conclusions
Lp-PLA2 changes in function of obesity, and that it shows important associations with markers of cardiovascular risk, in particular with waist circumference, glucose, HDL size and Apo B/Apo AI ratio. These results suggest that Lp-PLA2 activity can be a cardiovascular biomarker in adolescence.
Lipoprotein associated phospholipase A2 (Lp-PLA2) overexpression is implicated in athero-sclerosis. In the present study, we evaluated the effects of lentiviral-mediated RNA interference (RNAi) of Lp-PLA2 on inflammation and atherosclerosis in apolipoprotein E-deficient mice. Apolipoprotein E-deficient mice were randomly allocated to control and experimental groups, and constrictive collars were used to induce plaque formation. Eight weeks after surgery, the lentiviral-mediated RNAi construct was used to silence expression of Lp-PLA2. Control and experimental lentivirus was transfected directly into carotid plaques or administered systemically. Tissues were collected for analysis 7 weeks after transfection. Inflammatory gene expression in the plasma and atherosclerotic lesions was then determined at the mRNA and protein levels. We observed no differences in body weight and plasma lipid levels at the end of the investigation. However, the expression levels of Lp-PLA2 and pro-inflammatory cytokines were significantly reduced in the RNAi groups, compared to the controls, whereas the plasma concentration of anti-inflammatory cytokines was markedly increased. Moreover, our results demonstrated a significant reduction in plaque area and lipid content, as well as a rise in collagen content following RNAi treatment. Importantly, when comparing the two methods of viral delivery, we found that transluminal local transfection exhibited enhanced improvement of plaque stability as compared to systemic administration. Inhibition of Lp-PLA2 by lentiviral-mediated RNAi ameliorates inflammation and atherosclerosis in apolipoprotein E-deficient mice. In addition, transluminal local delivery of Lp-PLA2 shRNA is superior to systemic administration for stabilizing atherosclerotic plaques.
